Post-Myocardial Infarction Remodeling and Hyperkinetic Remote Myocardium in Sheep Measured by Cardiac MRI Feature Tracking.

BACKGROUND: Cardiac MRI feature tracking (FT) allows objective assessment of segmental left ventricular (LV) function following a myocardial infarction (MI), but its utilization in sheep, where interventions can be tested, is lacking. PURPOSE: To apply and validate FT in a sheep model of MI and describe post-MI LV remodeling. STUDY TYPE: Animal model, longitudinal. ANIMAL MODEL: Eighteen lambs (6 months, male, n = 14; female, n = 4; 25.2 ± 4.5 kg). FIELD STRENGTH/SEQUENCE: Two-dimensional balanced steady-state free precession (bSSFP) and 3D inversion recovery fast low angle shot (IR-FLASH) sequences at 3 T. ASSESSMENT: Seven lambs underwent test-retest imaging to assess FT interstudy reproducibility. MI was induced in the remaining 11 by coronary ligation with MRI being undertaken before and 15 days post-MI. Injury size was measured by late gadolinium enhancement (LGE) and LV volumes, LV mass, ejection fraction (LVEF), and wall thickness (LVWT) were measured, with FT measures of global and segmental radial, circumferential, and longitudinal strain. STATISTICAL TESTS: Sampling variability, inter-study, intra and interobserver reproducibility were assessed using Pearson's correlation, Bland-Altman analyses, and intra-class correlation coefficients (ICC). Diagnostic performance of segmental strain to predict LGE was assessed using receiver operating characteristic curve analysis. Significant differences were considered P < 0.05. RESULTS: Inter-study reproducibility of FT was overall good to excellent, with global strain being more reproducible than segmental strain (ICC = 0.89-0.98 vs. 0.77-0.96). MI (4.0 ± 3.7% LV mass) led to LV remodeling, as evident by significantly increased LV volumes and LV mass, and significantly decreased LVWT in injured regions, while LVEF was preserved (54.9 ± 6.9% vs. 55.6 ± 5.7%; P = 0.778). Segmental circumferential strain (CS) correlated most strongly with LGE. Basal and mid- CS increased significantly, while apical CS significantly decreased post-MI. DATA CONCLUSION: FT is reproducible and compensation by hyperkinetic remote myocardium may manifest as overall preserved global LV function. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 2.

Reintervention Before Bidirectional Cavopulmonary Shunt and Intermediate Outcomes in Children with Single Ventricle Who Underwent Main Pulmonary Artery Banding.

Unplanned reinterventions following pulmonary artery banding (PAB) in single ventricle patients are common before stage 2 palliation (S2P) but associated risk factors are unknown. We hypothesized that reintervention is more common when PAB is placed at younger age and with a looser band, reflected by lower PAB pressure gradient. Retrospective single center study of single ventricle patients undergoing PAB between Jan 2000 and Dec 2020. The association with reintervention and successful S2P was modeled using exploratory cause-specific hazard regression. A multivariable model was developed adjusting for clinical and statistically relevant predictors. The cumulative proportion of patients undergoing reintervention were summarized using a competing risk model. 77 patients underwent PAB at median (IQR) 47 (24-66) days and 3.73 (3.2-4.5) kg. Within18 months of PAB, 60 (78%) reached S2P, 9 (12%) died, 1 (1%) transplanted and 7 (9%) were alive without S2P. Within 18 months of PAB 10 (13%) patients underwent reintervention related to pulmonary blood flow modification: PAB adjustment (n = 6) and conversion to Damus-Kaye-Stansel/Blalock-Taussig-Thomas shunt (n = 4). 6/10 (60%) reached S2P following reintervention. A trend toward higher intervention in patients with a genetic syndrome (p-0.06) and weight < 3 kg (p-0.057) at time of PAB was noted. Only genetic syndrome was a risk factor associated with poor outcome (p-0.025). PAB has a reasonable outcome in SV patients with unobstructed systemic and pulmonary blood flow, but with a high reintervention rate. Only a quarter of patients with genetic syndromes reach S2P and further study is required to explore the benefits from an alternative palliative strategy.

Comparison between Del Nido and conventional blood cardioplegia in pediatric open-heart surgery.

BACKGROUND: Del Nido cardioplegia (DNc) was designed for superior myocardial protection during cardiopulmonary bypass (CPB). We conducted a retrospective review to explore if DNc was associated with increase in systemic ventricle dysfunction (sVD) following pediatric CPB. METHODS AND RESULTS: This single-center, retrospective study included 1534 patients undergoing CPB between 2013 and 2016, 997 prior to center-wide conversion to DNc and 537 following. The primary outcome was new postoperative ≥moderate sVD by echocardiogram. Secondary outcomes included sVD of any severity and right ventricular dysfunction. Data was evaluated by interrupted time-series analysis. Groups had similar cardiac diagnoses and surgical complexity. Del Nido cardioplegia was associated with longer median (IQR) CPB [117 (84-158) vs 108 (81-154), p = 0.04], and aortic cross-clamp [83 (55-119) vs 76 (53-106), p = 0.03], and fewer cardioplegia doses [2 (1-2) vs 3 (2-4), p < 0.0001]. Mortality was similar in both groups. Frequency of sVD was unchanged following DNc, including predetermine subgroups (neonates, infants, and prolonged cross-clamp). Logistic regression showed a significant rise in right ventricular dysfunction (OR 5.886 [95% CI: 0.588, 11.185], p = 0.03) but similar slope. CONCLUSIONS: Use of DNc was not associated with increased in reported sVD, and provided similar myocardical protection to the systemic ventricle compared to conventional cardioplegia but may possibly impact right ventricular function. Studies evaluating quantitative systolic and diastolic function are needed.

Impact of serial measurements of tricuspid annular plane systolic excursion on mortality and morbidity after heart transplantation.

The impact of right ventricular (RV) dysfunction on long-term post-HTx outcomes remains uncertain. We assessed the impact of serial measurements of Tricuspid Annular Plane Systolic Excursion (TAPSE) on post-HTx mortality and morbidity. This two-center retrospective cohort study included consecutive adult HTx recipients (2000-2017). We used multivariable extended hazard regression models to evaluate the association between TAPSE and left ventricular ejection fraction (LVEF), entered as time-dependent variables, and all-cause mortality, cardiac allograft vasculopathy (CAV), acute cellular rejection (ACR), and chronic kidney disease (CKD). TAPSE was modelled using cubic splines. We included 485 HTx recipients (9461 TAPSE measurements), median (25th- 75th percentile) 19 (10-27) mm; median age was 52 (41-59) years, and 71.3% were male. During a follow-up of 6.7 (3.0-10.8) years, 92 patients died, 225 had ACR >2R, 234 CAV, and 91 CKD. By multivariable analysis, for each 1-mm decrease in patients with a TAPSE value <15mm, mortality increased by 22% (P<.001). For the average HTx recipient with a TAPSE of 15mm, 10mm, and 6mm, 1-year mortality was 3%, 7%, and 17%, and 5-year mortality was 8%, 20%, and 43%, respectively. Reduced TAPSE was significantly associated with increased CAV but notACR and CKD. A decrease in TAPSE below 15mm represents clinically significant graft dysfunction, warranting close monitoring.

Predicted heart mass for size matching in obese heart transplant donors and recipients.

INTRODUCTION: Predicted heart mass (PHM) was neither derived nor evaluated in an obese population. Our objective was to evaluate size mismatch using actual body weight or ideal body weight (IBW)-adjusted PHM on mortality and risk assessment. METHODS: We conducted a retrospective cohort study of adult recipients with BMI ≥30 kg/m2 or recipients of donors with BMI≥30 kg/m2 from the ISHLT registry. We used multivariable Cox proportional hazard models to evaluate 30-day and 1-year mortality. The two models were compared using net reclassification index. RESULTS: 10,817 HT recipients, age 55 (IQR 46-62) years, 23% female, BMI 31 kg/m2 (IQR 28-33) were included. Donors were age 34 (IQR 24-44) years, 31% female, and BMI 31 kg/m2 (IQR 26-34). There was a significant nonlinear association between mortality and actual PHM but not IBW-adjusted PHM. Undersizing using actual PHM was associated with higher 30-day and 1-year mortality (p < .01), not seen with IBW-adjusted PHM. Actual PHM better risk classified .6% (95% CI .3-.8) patients compared to IBW-adjusted PHM. CONCLUSION: Actual PHM can be used for size matching when assessing mortality risk in obese recipients or recipients of obese donors. There is no advantage to re-calculating PHM using IBW to define candidate risk at the time of organ allocation.

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. METHODS: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy <18 years of age at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest, and aborted SCD, that is, appropriate shock following primary prevention implantable cardioverter defibrillators. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with 10 repeated 4-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized by using the c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe [Sarcomeric Human Cardiomyopathy Registry], n=285). RESULTS: Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated sudden cardiac arrests, and 14 aborted SCD). Risk predictors included age at diagnosis, documented nonsustained ventricular tachycardia, unexplained syncope, septal diameter z-score, left ventricular posterior wall diameter z score, left atrial diameter z score, peak left ventricular outflow tract gradient, and presence of a pathogenic variant. Unlike in adults, left ventricular outflow tract gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated between patients with and without SCD events with a c-statistic of 0.75 and 0.76, respectively, and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72, respectively). CONCLUSION: Our study provides a validated SCD risk prediction model with >70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.

Association between genetic variants in the HIF1A-VEGF pathway and left ventricular regional myocardial deformation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Information on genetic etiology of pediatric hypertrophic cardiomyopathy (HCM) rarely aids in risk stratification and prediction of disease onset. Little data exist on the association between genetic modifiers and phenotypic expression of myocardial performance, hampering an individual precision medicine approach. METHODS: Single-nucleotide polymorphism genotyping for six previously established disease risk alleles in the hypoxia-inducible factor-1α-vascular endothelial growth factor pathway was performed in a pediatric cohort with HCM. Findings were correlated with echocardiographic parameters of systolic and diastolic myocardial deformation measured by two-dimensional (2-D) speckle-tracking strain. RESULTS: Twenty-five children (6.1 ± 4.5 years; 69% male) with phenotypic and genotypic (60%) HCM were included. Out of six risk alleles tested, one, VEGF1 963GG, showed an association with reduced regional systolic and diastolic left ventricular (LV) myocardial deformation. Moreover, LV average and segmental systolic and diastolic strain and strain rate were significantly reduced, as assessed by the standardized difference, in patients harboring the risk allele. CONCLUSIONS: This is the first study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial function, with the VEGF1 963GG allele associated with reduced LV systolic and diastolic myocardial performance. While studies are needed to link this information to adverse clinical outcomes, this knowledge may help in risk stratification and patient management in HCM. IMPACT: Risk allele in the VEGF gene impacts on LV myocardial deformation phenotype in children with HCM. LV 2-D strain is significantly reduced in patients with risk allele compared to non-risk allele patients within HCM patient groups. Describes that deficiencies in LV myocardial performance in children with HCM are associated with a previously identified risk allele in the angiogenic transcription factor VEGF. First study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial deformation measured by 2-D strain in children with HCM.

Post-transplant survival in adult congenital heart disease patients as compared to dilated and ischemic cardiomyopathy patients; an analysis of the thoracic ISHLT registry.

Previous studies have shown that adult congenital heart disease (ACHD) is associated with high early post-transplant mortality but improved long-term survival in comparison to the overall heart transplant population. We aimed to evaluate survival outcomes of ACHD in adult transplant recipient patients as specifically compared to ischemic (ICM) and dilated cardiomyopathy (DCM) groups. Adult heart transplant recipients between 2004 and 2014 were identified from the ISHLT registry. We used Kaplan-Meier analysis to evaluate overall survival, 1-year survival, and 1-year conditional survival among etiology groups and multivariable Cox proportional hazard (PH) models to assess the association between etiology of cardiomyopathy and 1-year and long-term all-cause mortality and cause-specific mortality. We included 30 130 heart transplant recipients. One-year survival was 78.3% in ACHD, 84.3% in ICM, and 86.2% in DCM patients (P < .001). By multivariable analysis, during first post-transplant year, ACHD and ICM patients were at significantly higher mortality risk than DCM. Adjusted post-transplant mortality risk, conditional on 1-year survival, was not statistically different in ACHD and DCM while ICM patients had 17% higher long-term mortality risk than DCM patients leading to overall worse outcomes in ICM patients. Therefore, ICM patients have poorer outcomes in comparison to both DCM and ACHD patients.

Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor-derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS). METHODS: Retrospective single-center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV. RESULTS: Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non-Caucasian race (HR = 1.98, p = .011), BMI < 18 kg/m2 (HR = 4.596, p = .042), longer ischemic time (HR = 1.374, p = .028), older donor age (HR = 1.158, p = .009), and rejection with hemodynamic compromise within the first year (HR = 2.858, p = .043). Prednisone discontinuation within 1 year was associated with a lower risk of CAV (HR 0.58 p = .047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p < .001). CONCLUSION: In patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.

Rapid Advancement in Enteral Nutrition Does Not Affect Systemic Inflammation and Insulin Homeostasis Following Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: To determine impact of enteral nutrition delivery on the relationship among inflammation, insulin resistance, and outcomes following pediatric cardiopulmonary bypass surgery. DESIGN: Pilot, randomized study analyzed according to intention-to-treat analysis. SETTING: Pediatric cardiac ICU. PATIENTS: Infants (≤ 6 mo) undergoing cardiopulmonary bypass. INTERVENTIONS: Patients randomly assigned to receive rapid escalation to enteral nutrition reaching goal feeds by 27 hours or standard feeding practice reaching goal feeds by 63 hours. Feeds were initiated on the first postoperative day. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized equally to study arms. Patients were a median (interquartile range) of 16 days old (7-110 d old), undergoing biventricular surgery (88%) with a median cardiopulmonary bypass time of 125 minutes (105-159 min). Serial blood samples were drawn before and after cardiopulmonary bypass, cardiac ICU admission, and every 12 hours (up to 96 hr) for glucose, insulin, and cytokines (interleukin-1α, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) levels. Glucose-insulin ratio was calculated to quantify insulin resistance. Patient characteristics, time to enteral nutrition initiation, enteral nutrition interruptions, and insulin administration were similar across intervention arms. FF reached goal feeds at similar intervals as standard feeding (39 hr [30-60 hr] vs 60 hr [21-78 hr]; p = 0.75). No difference in cytokine, insulin, or glucose-insulin ratio was noted between groups. Higher inflammation was associated with increased glucose-insulin ratio and higher risk of adverse events. In multivariable models of interleukin-8, FF was associated with increased glucose-insulin ratio (estimate of effect [95% CI], 0.152 [0.033-0.272]; p = 0.013). Although higher interleukin-8 was associated with an elevated risk of adverse event, this relationship was possibly mitigated by FF (odds ratio [95% CI], 0.086 [0.002-1.638]; p = 0.13). CONCLUSIONS: A FF strategy was not associated with changes to early enteral nutrition delivery. Inflammation, insulin resistance, and morbidity were similar, but FF may modify the relationship between inflammation and adverse event. Multicenter nutrition studies are possible and necessary in this vulnerable population.

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry.

Sudden cardiac death (SCD) is responsible for ~10% of post-heart transplant deaths. We conducted a retrospective analysis of the ISHLT registry evaluating the risk of post-transplant SCD. Adult heart transplant recipients (2004-2014) surviving the first year were included. We used multivariable multistate competing risk survival analysis to evaluate the impact of history of treated rejection and cardiac allograft vasculopathy (CAV) on SCD risk. We used a probabilistic analytical model and Monte Carlo simulation to estimate the impact of CAV severity and graft dysfunction on SCD. We included 25 242 recipients. During a median follow-up of 4.7 (2.3-7.0) years, 582 patients died suddenly. Treated rejection (HR 1.76, 95% CI 1.36-2.31) and CAV (HR 3.32, 95% CI 2.73-4.03) were important risk factors for SCD. The estimated SCD risk in patients with severe CAV without and with graft dysfunction was 3.2% (95% CI 2.0-4.6) and 5.4% (95% CI 3.8-7.0), respectively, at 2 years from the CAV diagnosis, and 4.9% (95% CI 3.4-6.5) and 8.0% (95% CI 6.1-10.0), respectively, in those who also had treated rejection. These results provide evidence that recipients with severe CAV and graft dysfunction or treated rejection are at clinically significant increased SCD risk. The benefit of ICD post-transplant remains uncertain.

The effect of pre-heart transplant body mass index on posttransplant outcomes: An analysis of the ISHLT Registry Data.

We evaluated the effect of pre-heart transplant body mass index (BMI) on posttransplant outcomes using the International Society for Heart and Lung Transplantation Registry. Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. We assessed 38 498 recipients from 2000 to 2014 stratified by pretransplant BMI. Ten-year survival was 56% in underweight, 59% in normal weight, 57% in overweight, 52% in obese class I, 54% in class II, and 47% in class III patients (P < 0.001). Mortality was increased in underweight (HR 1.29, 95% CI 1.24-1.35), obese class I (HR 1.19, 95% CI 1.13-1.26), class II (HR 1.20, 95% CI 1.08-1.32), and class III patients (HR 1.45, 95% CI 1.15-1.83). Obesity was independently associated with increased death from myocardial infarction, chronic rejection, infection, and renal dysfunction. An underweight BMI lead to increased death from infection, acute and chronic rejection, malignancy, and bleeding. Obese patients had a higher incidence of renal dysfunction, diabetes, stroke, acute rejection, cardiac allograft vasculopathy, and malignancy, and underweight recipients had increased acute rejection. We have shown that pretransplant obese and underweight patients have increased post-heart transplant mortality and morbidity. This has implications for candidate selection and posttransplant management.

De novo donor-specific HLA antibodies in heart transplantation: Do transient de novo DSA confer the same risk as persistent de novo DSA?

BACKGROUND: It is estimated that 25%-35% of heart transplant recipients develop de novo donor-specific antibodies (dnDSA). One factor that appears to play a role in clinical outcomes is DSA persistence. The objective of this study was to determine the incidence of transient and persistent dnDSA in a Canadian heart transplant population and to evaluate their impact on coronary allograft vasculopathy (CAV), graft function, and mortality. METHODS: A retrospective study of consecutive adult and transitioned pediatric heart transplant recipients (2008-2015) in Toronto was performed. Clinical demographics were collected prospectively. HLA antibody testing was performed using Luminex single antigen assays. In statistical analysis, dnDSA was modeled as a time dependent covariate. RESULTS: During a median follow-up of 4.1 years, dnDSA were detected in 42 (23%) with a median time to detection of 329 days (156-740); 27 (64%) developed persistent dnDSA. Persistent dnDSA conferred an increased risk of death with a HR 4.0 (95%CI 1.4-12.1) when adjusted recipient age, CAV, and cytomegalovirus status. CONCLUSIONS: Transient dnDSA were not associated with adverse outcomes after heart transplantation. This suggests that transient dnDSA may not require enhanced immunosuppression, increased HLA antibody monitoring, or additional physiological assessment. By knowing the transient dnDSA status, clinicians may minimize both recipient morbidity and cost without increasing harm.

Incidence and predictors of sudden cardiac death after heart transplantation: A systematic review and meta-analysis.

PURPOSE: Sudden cardiac death (SCD) is an important post-transplant problem being responsible for ~10% of deaths. We conducted a systematic review and meta-analysis to evaluate incidence and predictors of post-heart transplant SCD and the use of implantable cardiac defibrillator (ICD). METHODS: Citations were identified in electronic databases and references of included studies. Observational studies on adults reporting on incidence and predictors of post-transplant SCD and ICD use were selected. We meta-analyzed SCD in person-years using random effects models. We qualitatively summarized predictors. RESULTS: This study includes 55 studies encompassing 47 901 recipients. The pooled incidence rate of SCD was 1.30 per 100 person-years (95% CI: 1.08-1.52). Cardiac allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100 patient-years, 95% CI: 1.46-3.34). Independent predictors of SCD identified by two moderate-quality studies were older donor age, younger recipient age, non-Caucasian race, reduced left ventricular ejection fraction, rejection, infection, and cancer. Authors rarely reported on ICD use. CONCLUSION: This meta-analysis found that post-transplant SCD risk in heart transplant recipients is higher than that in the general population. CAV was associated with increased SCD risk. Observational studies reporting on absolute risk of SCD are needed to better identify populations at a clinically significant increased risk.

Exercise Capacity and Self-Efficacy are Associated with Moderate-to-Vigorous Intensity Physical Activity in Children with Congenital Heart Disease.

This study sought to determine whether exercise capacity, self-efficacy, and gross motor skills are associated with moderate-to-vigorous physical activity (MVPA) levels in children, and if these associations differ by congenital heart disease (CHD) type. Medical history was abstracted from chart review. We assessed MVPA levels (via accelerometry), percent-predicted peak oxygen consumption ([Formula: see text] cardiopulmonary exercise test), gross motor skill percentiles (test of gross motor development version-2), and self-efficacy [children's self-perceptions of adequacy and predilection for physical activity scale (CSAPPA scale)]. CHD patients (n = 137, range 4-12 years) included children with a repaired atrial septal defect (n = 31, mean ± standard deviation MVPA = 454 ± 246 min/week), transposition of the great arteries after the arterial switch operation (n = 34, MVPA = 423 ± 196 min/week), tetralogy of Fallot after primary repair (n = 37, MVPA = 389 ± 211 min/week), or single ventricle after the Fontan procedure (n = 35, MVPA = 405 ± 256 min/week). MVPA did not differ significantly between CHD groups (p = 0.68). Higher MVPA was associated with a higher percent-predicted [Formula: see text] (EST[95% CI] = 16.9[-0.2, 34] MVPA min/week per 10% increase in percent-predicted [Formula: see text] p = 0.05) and higher self-efficacy (EST[95% CI] = 5.2[1.0, 9.3] MVPA min/week per 1-unit increase in CSAPPA score, p = 0.02), after adjustment for age, sex, and testing seasonality, with no association with CHD type. Higher MVPA was not associated with gross motor skill percentile (p = 0.92). There were no significant interactions between CHD type and percent-predicted [Formula: see text] self-efficacy scores, and gross motor skill percentiles regarding their association with MVPA (p > 0.05 for all). Greater MVPA was associated with higher exercise capacity and self-efficacy, but not gross motor skills.

Clinical Impact of Stent Implantation for Coarctation of the Aorta with Associated Hypoplasia of the Transverse Aortic Arch.

The aim of this study was to explore the clinical impact of transverse aortic arch hypoplasia (TAH) after stent implementation for isthmal coarctation of the aorta (CoA). From a retrospective chart review, 51 children (median age 11.1 years) were identified who had TAH and a CoA stent implanted between 10/1995 and 4/2015. Arm-leg cuff blood pressure measurements, echocardiographic arch imaging, and 24-h ambulatory blood pressure monitoring, prior to and after stent implantation, were reviewed. At catheterization, peak systolic gradients across the CoA's were 25 mmHg before and 4 mmHg after stent implantation. At a median 37-month follow-up, echocardiographic imaging showed no significant catch-up growth in the transverse arch (median z-score; proximal and distal arch -1.54 and -1.99 vs. -1.78 and -1.63, p = 0.13 and 0.90). A trend to increasing systolic blood pressure (SBP) differentials between the right and left arms was noted (11 mmHg [prior to]; 16 mmHg [follow-up], p = 0.09). Age-adjusted percentiles for right arm SBP decreased from 99.7% prior to, and 87.6% in follow-up (p < 0.001). The median time to re-intervention was 5.6 years (95% CI [2.8, 7.8]) and the proportion of children using anti-hypertensive in follow-up was not significantly different before the implantation (38% [prior to]; 45% [follow-up]). Elevated right arm blood pressure persists after successful stent implantation in the setting of associated TAH and there appears to be no catch-up growth of the transverse arch with time. Medical management can be difficult and approaches to surgical arch augmentation or stent implantation should be considered to avoid unilateral arm hypertension.

Reported electronic cigarette use among adolescents in the Niagara region of Ontario.

BACKGROUND: Use of electronic cigarettes (e-cigarettes) among adolescents has not been fully described, in particular their motivations for using them and factors associated with use. We sought to evaluate the frequency, motivations and associated factors for e-cigarette use among adolescents in Ontario. METHODS: We conducted a cross-sectional study in the Niagara region of Ontario, Canada, involving universal screening of students enrolled in grade 9 in co-operation with the Heart Niagara Inc. Healthy Heart Schools' Program (for the 2013-2014 school year). We used a questionnaire to assess cigarette, e-cigarette and other tobacco use, and self-rated health and stress. We assessed household income using 2011 Canadian census data by matching postal codes to census code. RESULTS: Of 3312 respondents, 2367 answered at least 1 question in the smoking section of the questionnaire (1274 of the 2367 respondents [53.8%] were male, with a mean [SD] age of 14.6 [0.5] yr) and 2292 answered the question about use of e-cigarettes. Most respondents to the questions about use of e-cigarettes (n = 1599, 69.8%) had heard of e-cigarettes, and 380 (23.8%) of these respondents had learned about them from a store sign or display. Use of e-cigarettes was reported by 238 (10.4%) students. Most of the respondents who reported using e-cigarettes (171, 71.9%) tried them because it was "cool/fun/new," whereas 14 (5.8%) reported using them for smoking reduction or cessation. Male sex, recent cigarette or other tobacco use, family members who smoke and friends who smoke were strongly associated with reported e-cigarette use. Reported use of e-cigarettes was associated with self-identified fair/poor health rating (odds ratio [OR] 1.9 (95% confidence interval [CI] 1.2-3.0), p < 0.001), high stress level (OR 1.7 (95% CI 1.1-2.7), p < 0.001) and lower mean (33.4 [8.4] × $1000 v. 36.1 [10.7] × $1000, p = 0.001) and median [interquartile range] (26.2 [5.6] × $1000 v. 28.1 [5.7] × $1000) household incomes. INTERPRETATION: Use of e-cigarettes is common among adolescents in the Niagara region and is associated with sociodemographic features. Engaging in seemingly exciting new behaviours appears to be a key motivating factor rather than smoking cessation.

Association between gastrointestinal events and osteoporosis treatment initiation in women diagnosed with osteoporosis in France: a retrospective analysis.

BACKGROUND: A substantial portion of women diagnosed with osteoporosis (OP) do not initiate pharmacotherapy to reduce fracture risk. In clinical practice, gastrointestinal (GI) events have been linked with OP therapy discontinuation. However, there is limited research examining GI events as barrier to treatment initiation following an OP diagnosis. The objective of this study was to examine the association between gastrointestinal (GI) events and osteoporosis (OP) treatment initiation among post-menopausal women diagnosed with osteoporosis in France. METHODS: A retrospective claims analysis of the Mediplus France database during 1997 to 2010 identified women aged ≥ 55 with an OP diagnosis and without prior OP treatment (first diagnosis date was defined as the index date). GI events were identified during the 1 year pre-index and up to 1 year post-index. OP treatment initiation post-index was identified based on the presence of claims for any bisphosphonate (BIS) or non-BIS OP medication within 1 year post-index. Multivariate models (logistic regression, Cox proportional hazards regression and discrete choice) adjusted for pre-index patient characteristics were used to assess the association of pre- and post-index GI events with the likelihood of initiating OP treatment, and the type of treatment initiated (BIS vs. non-BIS). RESULTS: A total of 10,292 women (mean age 70.3 years) were identified; only 25% initiated OP treatment. Post-index GI events occurred in 11.5% of patients, and were associated with a 75.7% lower likelihood of initiating OP treatment. Among treated patients, a discrete choice model estimated that patients with post-index GI events were 34.6% less likely to receive BIS vs non-BIS as compared to patients without post-index GI events. CONCLUSION: Among women aged ≥ 55 years with an OP diagnosis, post-index GI events were associated with a lower likelihood of OP treatment initiation.

Mitral valve surgery in patients with Marfan syndrome.

OBJECTIVE: To review the pathology of the mitral valve (MV) and long-term outcomes of surgery in patients with Marfan syndrome (MFS). PATIENTS AND METHODS: From 1988 through 2020, 60 patients with MFS had surgery to correct mitral regurgitation (MR): 19 had isolated MV surgery, 32 had combined MV and aortic root surgery, and 9 had MV surgery after aortic root surgery. Follow-up was complete for a median of 16.1 years. RESULTS: MV pathology was myxomatous degeneration in all patients and of advanced degree in 78.6% with bileaflet prolapse in 65.5%, mitral annulus disjunction in 57.5%, and mitral annulus calcification in 8.2% of patients. The MV was repaired in 47 patients and replaced in 13. Kaplan-Meier estimates of cumulative mortality at 20 years 21.3% for all patients, 6.7% after MV repair, and 57.8% after replacement (P < .001). MV reoperations were performed in 5 patients: 2 after repair and 3 after replacement. The cumulative incidence rate of reoperations on the MV was 3.8% at 10 years and 11.0% at 20 years in the entire cohort. Among 47 patients who had MV repair, moderate MR developed in 11 patients and severe in 2. Both patients with severe MR underwent MV reoperation. The cumulative incidence rate of recurrent moderate or severe MR after MV repair was 20.4% at 10 years, and 36.5% at 20 years. CONCLUSIONS: MV repair was associated with better survival than MV replacement, but recurrent MR after repair occurred in approximately one-third of the patients at 20 years after surgery.

Safety of Continuing Trastuzumab for Mild Cardiotoxicity: A Cardiovascular Magnetic Resonance Imaging Study.

The safety of continuing human epidermal growth factor receptor 2 (HER2)-targeted therapy in women with mild cardiotoxicity remains unclear. We performed a retrospective matched cohort study of 14 patients with human epidermal growth factor receptor 2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, nested within the Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI (EMBRACE-MRI) trial. Among patients who developed cardiotoxicity and were treated with heart failure therapy, we compared those who had trastuzumab therapy interrupted to a matched cohort who continued trastuzumab therapy. By a median of 2.5 years of follow-up, no significant differences were present between the groups in the proportion with magnetic resonance imaging-measured left ventricular ejection fraction < 40%, magnetic resonance imaging-measured left ventricular volumes, left ventricular ejection fraction, edema, fibrotic markers, cardiopulmonary fitness, or quality of life.

La question de savoir s'il est sûr de poursuivre le traitement par un médicament ciblant le récepteur 2 du facteur de croissance épidermique humain (HER2) en présence d'une légère cardiotoxicité chez la femme demeure controversée. Nous avons réalisé une étude de cohortes appariées rétrospective auprès de 14 patientes atteintes d'un cancer du sein positif pour le HER2 qui recevaient un traitement séquentiel par l'anthracycline et le trastuzumab, dans le cadre du programme EMBRACE-MRI ( E valuation of M yocardial Changes During Br east A denocarcinoma Therapy to Detect C ardiotoxicity E arlier With MRI ). Parmi les patientes ayant développé une cardiotoxicité et ayant reçu un traitement pour l'insuffisance cardiaque, nous avons comparé celles dont le traitement par le trastuzumab a été interrompu à une cohorte appariée ayant poursuivi ce traitement. Après un suivi médian de 2,5 ans, aucune différence significative n'avait été observée entre les groupes en ce qui concerne le pourcentage de patientes dont la fraction d'éjection ventriculaire gauche était inférieure à 40 % à l'imagerie par résonance magnétique (IRM), le volume ventriculaire gauche à l'IRM, la fraction d'éjection ventriculaire gauche, l'œdème, les marqueurs fibrotiques, la bonne forme physique de l'appareil cardio-pulmonaire ou la qualité de vie.